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Abstract:

We use an Atomic Force Microscope based single molecule measurements to evaluate the activation free energy in the interaction of SNARE proteins syntaxin 1A, SNAP25B and synaptobrevin 2 which regulate intracellular fusion of vesicles with target membranes. The dissociation rate of the binary syntaxin-synaptobrevin and the ternary syntaxin-SNAP25B-synaptobrevin complex was measured from the rupture force distribution as a function of the rate of applied force. The temperature dependence of the spontaneous dissociation rate was used to obtain the activation energy to the transition state of 19.8±3.5 kcal/mol = 33±6 kBT and 25.7±3.0 kcal/mol = 43±5 kBT for the binary and ternary complex, respectively. They are consistent with those measured previously for the ternary complex in lipid membranes and are of order expected for bilayer fusion and pore formation. The ΔG was 12.4–16.6 kcal/mol = 21–28 kBT and 13.8–18.0 kcal/mol = 23–30 kBT for the binary and ternary complex, respectively. The ternary complex was more stable by 1.4 kcal/mol = 2.3 kBT, consistent with the spontaneous dissociation rates. The higher adhesion energies and smaller molecular extensions measured with SNAP25B point to its possible unique and important physiological role in tethering/docking the vesicle in closer proximity to the plasma membrane and increasing the probability for fusion completion.

Recent advances in nanomaterials indicates that the central nervous system (CNS) is susceptible to nanoparticle induced alterations leading to functional or structural alterations. This knowledge is currently disseminated in vast array of journals dealing with broad subject areas related to pharmacology, toxicology, neuroscience or nanosciences. Thus, there is an urgent need to collect all these diverse information related to nanoscience and brain function in one place using Journal of Nanoneuroscience for the benefit of the scientific community, researchers, health planners, health care providers, policy makers, environmentalists, biologists, chemists, and physicist in this emerging area of medical science.